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Article Abstract

Benzodiazepines bind to a specific site on the γ-aminobutyric acid (GABA)-benzodiazepine receptor
complex. This complex has been implicated in the pathophysiology of anxiety by numerous preclinical
and clinical studies. Preclinical studies have shown that there are multiple molecular forms of
this receptor complex, that these genetically coded variations are linked to specific actions of the benzodiazepines,
and that receptors are located in neuroanatomical areas known to mediate the anxiety
response in animals and humans. Human studies have shown that patients with pathologic anxiety
have anomalous responses to drugs that specifically bind to these receptors and have reduced numbers
of benzodiazepine receptors in key brain areas that regulate anxiety responses. More recent preclinical
studies suggest that molecular alterations in this receptor complex may produce findings in animals
similar to those observed in anxious humans. Finally, chronic treatment with benzodiazepines causes
the development of tolerance, which may be associated with molecular changes and a pharmacologic
response profile similar to that observed in pathologically anxious humans.